An inflammatory response is one of the human immune systems activated by various action mechanisms to defend against physical actions, chemicals, bacterial infections, or immunological stimuli, which are applied to living organisms or tissue. However, when such inflammatory response persists, rather, damage to a mucous membrane is promoted, and therefore it has been noted that inflammatory diseases including rheumatoid arthritis, atherosclerosis, gastritis, asthma, etc. are caused by erythema, a fever, swelling, pain, or dysfunction. Such an inflammatory response is classified into acute inflammation and chronic inflammation as time passes. The acute inflammation is an inflammatory response lasting several days to several weeks, and causes a symptom such as erythema, a fever, pain, or swelling, whereas the chronic inflammation is a long-term inflammatory state for several years to decades, and involves a histological change such as fibrosis or the destruction of tissue caused by the infiltration of monocytes, proliferation of fibroblasts or capillaries, or an increase in connective tissue.
Specifically, when inflammatory stimuli are applied to the living organism, locally, histamine, bradykinin, prostaglandins, nitric oxide (NO), all types of pro-inflammatory cytokines, etc. are synthesized and secreted, and cause erythema, a fever, pain, or swelling as well as vasodilation. Particularly, in inflammation in the body, in addition to common immune factors, for example, cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin E2 (PGE2) are well known as major proinflammatory materials.
Conventionally, the termination of an inflammation response is known as a phenomenon naturally and passively occurring due to a decrease in levels of materials initiating inflammation, but it was found that the termination of inflammation is actively promoted by lipoxins, resolvins, or protectins, which were discovered by Serhan et al., like prostaglandins, which are involved in the initiation of inflammation. For example, it has been reported that Resolvin E1 is effective for pain, and RvE1 induces the termination of inflammation and is effective in treating an allergic inflammatory disease. In addition, it has been reported that low levels of factors actively promoting the termination of such inflammation in a chronic inflammatory disease, that is, lipoxin A4 and lipoxin induced by aspirin are shown in asthmatic patients and atherosclerotic patients.
Accordingly, while various attempts to find novel materials for inducing the termination of inflammation and thus to treat diseases associated with abnormal inflammation termination have been made (Korean Unexamined Patent Application No. 10-2015-0011875), a compound known to be included in lipoxins, resolvins, etc. is metabolically unstable and thus rapidly degraded in the body due to several double bonds in its structure, and is somewhat difficult to be developed as a drug by mass production of a material, thereby having a great problem in drugability.
Meanwhile, leukotriene B4 (LTB4) is a group of inflammatory lipid mediators synthesized from arachidonic acid (AA) via a 5-lipoxygenase pathway mediating acute and chronic inflammation. LTB4 is known to give a biological effect by binding to two types of receptors such as BLT1 and BLT2. Leukotriene B4 receptor 2 (BLT2), as one among the G protein-coupled receptor (GPCR) family, is a receptor having low affinity to LTB4, and a lipid mediator of arachidonic acid (AA) induced via a 5-lipoxygenase-dependent pathway.
Accordingly, to solve the above-mentioned conventional problems, the inventors prepared a novel compound exhibiting a BLT2 inhibitory activity while conducting research to develop a material for inducing the effective termination of inflammation, and first invented a therapeutic agent for an inflammatory disease, which includes the above-mentioned compound.